Sunday, November 26, 2006

The Importance of Being Genetic

Before I get into the possible whys of homosexuality, it’s probably best to go into the topic of genetics.

(In the following an alteration needs to be made; I'd hope to know if it’s clear before you get to the end :-))

I first want point out how difficult it is to understand who we’re talking about in these studies. Are they people who identify as homosexual or choose homosexual actions? As Perelle et al. point out in their review, An International Study of Sexual Orientation: The Data (1):

“there is no agreement among researchers as to who can be considered a homosexual person, what is the etiology of homosexuality, or what the proportion of homosexuality is in the world's population”

By defining people by the actions they choose, we do find that just under 10% of the US population is homosexual (2). With such a high occurrence of homosexual behavior, one should expect a genetic role in the associated orientation. This fact has been readily accepted and without controversy, for many decades. As Rief explains way back in 1939 (my emphasis) (3):

“WHILE the occurrence of hetero- and homo-sexuality does not appear to conform to any simple Mendelian formula [a simple genetic mode of inheritance], the familial incidence of homosexuality rather definitely indicates a genetic basis.”

More recently, in a review by Orlebeke, 1996, we see this observation repeated with much supporting data (4). Simply, homosexuality clearly runs in families, and no serious researcher disputes that.

But finding the extent and mechanism of the involved gene or genes has been a bit of a problem. To do this and better separate nature from nurture, twin studies have typically been used.

Firstly, similar to what we saw in my past posts (here and here), gay twins also show a birth weight effect, as reported by Orlebeke et al. in a study of 1,700 twin pairs (4). They report “very low” birth weight correlated with homosexuality, and theorized that the “possibility that exposure to prenatal…hormones” made these children gay. These finding were repeated by James et al. in 2002 (5). It should also be noted that same-sex twins were more often gay than opposite sex twins (6).

But back to the genes in twin studies.

On the general topic, Sicotte et al., in 1999, did an excellent job of reviewing and compiling 28 studies, which represented almost 10,000 twin pairs (!), in “the largest meta-analysis of twins and singletons conducted to date” (I, of course, see no need to go into each study separately :-)) (7). They found, in part, for dizygotic twins (fraternal, not sharing the exact same genes) that if one twin were gay the other had a 9.4% chance of being gay themselves (choosing gay activities). This is about the same as the background, thus suggesting no upbringing effect, as the twins were raised together.

But, for monozygotic twins (twins who do share the same genetic code), the other twin had a 14.9% chance of being gay. So clearly they found a genetic effect. When a child shares the same genes as his brother, he’s about 1.6 times more likely to be gay himself.

Also clearly, with only a 15% concordance, genes are not the whole story. It’s clear this is where effects such as hormone exposure, immune response, and prenatal experience come in. Regardless, the authors conclude (my emphasis):

“Although the frequent occurrence of monozygotic twins who are discordant for sexual orientation is clearly inconsistent with genetic models that would define hetero and homosexuality as dominant or recessive traits, discordance among monozygotic twins does not automatically preclude straightforward inheritance of one or more genes that strongly influence sexual orientation.”

Sure, there are many discordant identical twins who do not share their brother or sister’s orientation, and there are some interesting findings regarding the non-gay sibling (8). Still, discordance, gratefully, causes no one to rule out a strong genetic effect or claim homosexuality is a chosen lifestyle.

But the genetic cause must be complicated, and a handful of studies bring to question the results of Sicotte, questioning the existence of any significant genetic cause. For example Derom, was unable to find any significant difference between monozygotic and dizygotic twins using 808 twin pairs (9), and a similar finding was reported by Ross in 1999 with over 2,000 twin pairs (10). Simply these two studies were unable to find any statistically significant difference between the appearance of homosexuality in fraternal and identical twins.

This apparent inconsistency in the data, coupled with the low concordance found even in studies purporting it, has lead prominent researchers in the field to refer to twin studies as the Achilles heal of the hypothesis of there being a genetic cause of homosexuality (11). Fortunately it really doesn’t matter much, not to homosexuals, not to the general public, not to politicians. While, in my dad’s day, they’d be persecuted for their behaviors, even by public school teachers in front of the whole class, no kid questions or tries to alter his orientation these days. It’s really only of interest to biologists and psychologist who care to study such things. And among them, even those questioning the genetic involvement know there is a biological reason involved and it would take willful ignorance and a denial of one’s own experience with sexuality to think homosexuality is a matter of choice.

…

Okay, enough. I must confess I stole this idea from a book I read a long while ago (but I put a lot more work into it :-)). In short, the above in this post only is false, and I hope you can see the reason I did it this way. None of those studies refer to what I say they do. To make it true, though, is quite easy: replace all references to sexual orientation with handedness, and those to homosexuality with left-handedness.

I’ll wait….

There, now this post true; look at the references if you don’t trust me ;-). But read it again and see how it sounds, all true, but now minus the political, social, and religious baggage we all, both sides, carry into the topic of homosexuality and issues of “born that way”.

As we’ll see in a future post, for a genetic role in being gay a shocking amount of the above applies (for example, the birth weight findings again), and where it deviates from handedness it deviates into the direction of homosexuality being more a matter of genes than handedness (perhaps surprising with the apparent difference in effect the two have with regards to reproduction). Both the biological parallels and differences are surprising to me, not to mention the political and social differences (which I just mentioned ;-)).

Again, I hope your trust doesn't feel betrayed in my trying to illustrate the importance of being genetic :-).

Okay, the most prominent theory here is one of a “right-shift” gene (or genes). Here the genetic influence doesn’t make one left-handed; the gene makes near all of those holding it right handed, or leave handedness greatly up to an apparently random process in the fetus, resulting in the normal distribution seen in the data. It’s a simple Mendelian rule of inheritance as well. So handedness is determined by a completely random, normal distribution, but the genes might push that distribution's mean to a point where there may be no significant chance for left-handedness.

The history of this hypothesis is presented by its creator in this review (1), which I’ve not read in it’s entirety, but I could email to you if you’re interested. It has much more supporting info than I’m willing to go over as I don’t care about the political implications of being left-handed :-). There’s also a book (2). For a bit of it:

“…That is, the relative proportions of left-, mixed-, and right-handers in humans and nonhumans were consistent with a normal distribution, which was symmetrical about 0 for nonhumans but displaced slightly to the right for humans. This was the “aha!” experience on which the RS theory was founded.”

So it seems there’s something extra in humans (and chimps, below) that moves the handedness distribution to the right (hand).

There is a good amount of data to back this up regarding brain structure. In the review Annett goes over evidence involving topics from lesions of the brain to dyslexia, and so on. For a more recent example to add to Annett’s review, one could look at Geschwind (3):

“…cerebral asymmetry is strongly correlated with handedness, and handedness does have a significant genetic component… we examined the volumes of left and right cerebral cortex in a large cohort of aging identical and fraternal twins and explored their relationship to handedness. Cerebral lobar volumes had a major genetic component, indicating that genes play a large role in changes in brain volume that occur with aging. Shared environment, which likely represents in utero events, had about twice the effect on the left hemisphere as on the right, consistent with less genetic control over the left hemisphere. To test the major genetic models of handedness and cerebral asymmetry, twin pairs were divided into those with two right handers and those with at least one left hander (nonright handers). Genetic factors contributed twice the influence to left and right cerebral hemispheric volumes in right-handed twin pairs, suggesting a large decrement in genetic control of cerebral volumes in the nonright-handed twin pairs. This…is consistent with models postulating a right-hand_left-hemisphere-biasing genetic influence, a ‘‘right-shift’’ genotype that is lost in nonright handers,resulting in decreased cerebral asymmetry.”

Also, in our chimp cousins, evidence of possible right shift genes have been found (4). I’ll not go into the data here but here’s a quote from the abstract:

“We report evidence that hand preferences in chimpanzees are heritable, even among related individuals raised in different environments. Furthermore, we report that the degree of heritability is modified by factors associated with developmental instability, notably, offspring parity.”

They also conclude that “The results…indicate that hand preferences in chimpanzees are probably genetically determined and most closely follow the predictions of the right shift model…” Chimps are about 2:1 right to left-handed, as compared to our 9:1. This leads them to believe a shared gene or set of genes will be found (now that we have the ability) that cause this right-shift effect.

In short, similar to the case for gays, this research is still progressing, but without all that nasty political aftertaste.

Drat! One last thing: Another finding I should have included in the main post was the fact that left handedness is less likely in females than in males, again, like homosexuality. A similar mechanism is proposed for both here as well.

Man, you are a thorough blogger. I seldom even use the spell checker (as I'm sure most people have noticed), let alone double-checking references and including a full bibliography.

It's not a surprise that a recent post of mine included a third-hand quote. Unverified. LOL!

Anyway, putting all the science-speak aside, the "shift" idea makes sense but still fails to assuage the folks who want a yes or no answer. "A strong genetic influence" could easily be made to look like causality. Which it isn't.

Eh, I wouldn’t be thorough on such posts if not for the fact that much of them are based on material I’ve had for years and/or stuff I plan to use in the future (I wouldn’t have caught that reference error if not for your comment either :-)). But regarding spell check, as you should well know my dear L, no one would listen to me if they knew my horrible spelling secret :-).

On the genetics of handedness: first, it should be noted that it’s not likely as simple as Annett hypothesizes. Though they do have a good deal of supporting data, there may still be room for other genetic influences, say, a gene that causes all who have it to be left-handed for a minority of southpaws and seen in some concordant twins. The fact that handedness runs in families, even of those raised away from their biological parents shows what they are calling this strong genetic influence.

Discordant twins confuse that influence, and that’s where the right shift comes in. But are you saying that’s not a significant genetic determinant of handedness?

Let’s make the right-shift as simple as possible, one gene, dominant or recessive:

So the unadulterated process gives humans a random handedness, as seen in other mammals as the normal, natural biological state. But with this RS gene randomness is pushed into right-handed. Would you consider that a “strong genetic influence on handedness”?

If you have that RS gene, your handedness is set to “right” by that, causality. If you have other genes, sure, your handedness is then completely random, but that distribution is still caused by the genes, if not for them your switch could not be set to “left”. For genes to cause A or to cause a 50/50 chance A or B still strikes me to think of it as a strong genetic influence.

This also gets back to the fuzziness between nurture and nature, and the fact that all things about us are ultimately dependent upon nature. The genes must set a mechanism in handed animal brains even if that mechanism is “toss the nano-dice” (you’ve at least have to have genes for hands and brains ;-)). There must be “dice” to toss, “eyes” to read the result, and then a “switch” to be set, in the genes, right?

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